Experiments will study induction of specific unresponsiveness to tissue allografts utilizing immunosuppression and donor antigen. Mice immunosuppresed with antilymphocyte serum (ALS) and injected with donor bone marrow are specifically unresponsive to donor antigens. This unresponsiveness is a type of active enhancement since mice bearing perfect grafts have recipient anti-donor, cell-mediated immunity (CMI) and serlogical blocking factors (SBF). Experiments will study the mechanism of active enhancement in immunosuppressed mice with reference to (i) the role of CMI and SBF in unresponsive states produced by different methods of immunosuppression and different donor antigens, (ii) the role of antigen density in the enhanced graft, and (iii) the effect of humoral antibody suppression on active enhancement. Studies on methods for induction of enhacement in cellular immunosuppressed mice will be performed to investigate the effect of donor antigen presensitization, the use of cryopreserved marrow, and the efficacy of whole blood as sensitizing and enhancing agent. These studies will develop methods which will be tested in experiments to produce active enhancement of renal allografts in immunosuppressed dogs. Dog studies are designd to produce methods for active enhancement production directly applicable to human transplantation. A study is planned to test the efficacy of specific cadaveric bone marrow infusion on survival of human cadaveric renal allografts in assciation with a standard immunosuppressive protocol. Other experiments will investigate the contributing effect of immunostimulation (graft survival) and/or immunosuppression (ALS therapy) on activation of certain murine oncogenic viruses. Because of the poor tolerance of diabetics to chronic immunosuppression, long-term transplantation of iseets without chronic immunosuppression is required. Active enhancement of islet cell allografts will be studied in immunosuppressed, diabetic mice.